title: Glutathione S-transferase M1 and T1 polymorphisms may predict adverse effects after therapy in children with medulloblastoma.
abstract: Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by radiation used to treat medulloblastoma. We hypothesized that GST polymorphisms may be responsible, in part, for individual differences in toxicity and responses in pediatric medulloblastoma. We investigated the relationship between GSTM1 and GSTT1 polymorphisms and survival and toxicity in 42 children with medulloblastoma diagnosed and treated at the Texas Children's Cancer Center. We conducted Kaplan-Meier analyses to determine if the GST polymorphisms were related to progression-free survival (PFS) and performed logistic regression to explore associations between GST polymorphisms and occurrence of grade 3 or greater (> or =Gr 3) myelosuppression, ototoxicity, nephrotoxicity, neurotoxicity, and intellectual impairment. Patients with at least one null genotype had a 4.3 (95% confidence interval, 1.1-16.8), 3.7 (1-13.6), and 6.4 (1.2-34) times increased risk for any > or =Gr 3 toxicity, any > or =Gr 3 toxicity excluding peripheral neuropathy, and any > or =Gr 3 toxicity requiring omission or cessation of chemotherapy, respectively. Compared with all others, patients with at least one null genotype had, on average, 27.2 (p x= 0.0002), 29 (p = 0.0004), and 21.7 (p = 0.002) lower full-scale, performance, and verbal intelligence quotient (IQ) scores, respectively. GSTM1 and GSTT1 polymorphisms may predict adverse events, including cognitive impairment after therapy, in patients with medulloblastoma. A larger study to validate these findings is under way.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Nadia
authors.initials: N
authors.lastname: Barahmani
authors.forename: Sarah
authors.initials: S
authors.lastname: Carpentieri
authors.forename: Xio-Nan
authors.initials: XN
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yumei
authors.initials: Y
authors.lastname: Cao
authors.forename: Laura
authors.initials: L
authors.lastname: Howe
authors.forename: Lindsay
authors.initials: L
authors.lastname: Kilburn
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.forename: Ching
authors.initials: C
authors.lastname: Lau
authors.forename: M Fatih
authors.initials: MF
authors.lastname: Okcu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000139:chemically induced / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: D005982:Glutathione Transferase; C413545:glutathione S-transferase T1